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. 2018 Jan 8;8:55. doi: 10.1038/s41598-017-18388-6

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Bace1 Inhibition recovers leptin sensitivity in DIO mice and reduces inflammation. Vehicle or M-3 (10 mg/kg) administered to (a,b) lean (n = 5–18/group) or (c,d) DIO (n = 7–14/group) mice for 5 days, each group given saline or leptin (2 mg/kg) twice daily for the last 3 days. Food intake (a,c) and % body weight change (b,d) at end of injection period. Hypothalamic pSTAT3^Tyr705 levels by ELISA for vehicle or M-3 treated mice receiving saline or leptin. (e) lean (n = 6–7/group) and (f) DIO (n = 7–8/group). (g) Hypothalamic levels of SOCS3, SOCS3 and PTP1B of DIO mice given vehicle or M-3 (n = 7–9, SOCS3 mRNA and protein; n = 5, PTP1B). (h,i) Relative cytokine levels of DIO hypothalamus after 14 days vehicle or sc M-3 (h) or icv M-3 (i) (n = 9–12/group). Data are means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by one-way ANOVA with Bonferroni’s multiple comparisons test (a–f) or 2-tailed unpaired Student’s t-test (g,h,i).